Sofie Carrette

Meropenem and piperacillin/tazobactam prescribing in critically ill patients: Does augmented renal clearance affect pharmacokinetic/pharmacodynamic target attainment when extended infusions are used?

BackgroundCorrect antibiotic dosing remains a challenge for the clinician. The aim of this study was to assess the influence of augmented renal clearance on pharmacokinetic/pharmacodynamic target attainment in critically ill patients receiving meropenem or piperacillin/tazobactam, administered as an extended infusion.MethodsThis was a prospective, observational, pharmacokinetic study executed at the medical and surgical intensive care unit at a large academic medical center. Elegible patients were adult patients without renal dysfunction receiving meropenem or piperacillin/tazobactam as an extended infusion. Serial blood samples were collected to describe the antibiotic pharmacokinetics. Urine samples were taken from a 24-hour collection to measure creatinine clearance. Relevant data were drawn from the electronic patient file and the intensive care information system.ResultsWe obtained data from 61 patients and observed extensive pharmacokinetic variability. Forty-eight percent of the patients did not achieve the desired pharmacokinetic/pharmacodynamic target (100% f T>MIC), of which almost 80% had a measured creatinine clearance >130 mL/min. Multivariate logistic regression demonstrated that high creatinine clearance was an independent predictor of not achieving the pharmacokinetic/pharmacodynamic target. Seven out of nineteen patients (37%) displaying a creatinine clearance >130 mL/min did not achieve the minimum pharmacokinetic/pharmacodynamic target of 50% f T>MIC.ConclusionsIn this large patient cohort, we observed significant variability in pharmacokinetic/pharmacodynamic target attainment in critically ill patients. A large proportion of the patients without renal dysfunction, most of whom displayed a creatinine clearance >130 mL/min, did not achieve the desired pharmacokinetic/pharmacodynamic target, even with the use of alternative administration methods. Consequently, these patients may be at risk for treatment failure without dose up-titration.

Technical aspects of neurostimulation: Focus on equipment, electric field modeling, and stimulation protocols

Neuromodulation is a field of science, medicine, and bioengineering that encompasses implantable and non-implantable technologies for the purpose of improving quality of life and functioning of humans. Brain neuromodulation involves different neurostimulation techniques: transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), vagus nerve stimulation (VNS), and deep brain stimulation (DBS), which are being used both to study their effects on cognitive brain functions and to treat neuropsychiatric disorders. The mechanisms of action of neurostimulation remain incompletely understood. Insight into the technical basis of neurostimulation might be a first step towards a more profound understanding of these mechanisms, which might lead to improved clinical outcome and therapeutic potential. This review provides an overview of the technical basis of neurostimulation focusing on the equipment, the present understanding of induced electric fields, and the stimulation protocols. The review is written from a technical perspective aimed at supporting the use of neurostimulation in clinical practice.

Responsive neurostimulation in epilepsy

Various neurostimulation modalities have emerged in the field of epilepsy. Despite the fact that delivery of an electrical current to the hyperexcitable epileptic brain might, at first, seem contradictory, neurostimulation has become an established therapeutic option with a promising efficacy and adverse effects profile. In “responsive” neurostimulation the strategy is to interfere as early as possible with the accumulation of seizure activity to prematurely abort or even prevent an upcoming seizure. The design of technology required for responsive stimulation is more challenging compared with devices for open-loop neurostimulation. The achievement of therapeutic success is dependent on adequate sensing and stimulation algorithms and a fast coupling between both. The benefits of delivering current only at the time of an approaching seizure merit further investigation. Current experience with responsive neurostimulation in epilepsy is still limited, but seems promising.

Repetitive Transcranial Magnetic Stimulation For The Treatment Of Refractory Epilepsy

ABSTRACT Introduction: Repetitive transcranial magnetic stimulation (rTMS) is an established non-invasive neurostimulation technique that is able to induce neuromodulatory effects outlasting the duration of the stimulation train. The cortical excitability disturbance in epilepsy provides a rationale for investigating the efficacy of low-frequency rTMS as a treatment for epilepsy patients. Sofar clinical trials in epilepsy patients have shown conflicting results ranging from ineffective to very effective. Areas covered: This manuscript provides an overview of the performed studies, retrieved from a PubMed search, and a critical appraisal of their results. A number of conclusions are drawn and potential optimization strategies are discussed. Expert commentary: Although the therapeutic efficacy of rTMS in refractory epilepsy has not yet been established, the non-invasiveness of the technique warrants further investigation of rTMS as a treatment for epilepsy.

A prestimulation evaluation protocol for patients with drug resistant epilepsy

Neurostimulation is making its way into the therapeutic armamentarium of the epileptologists, with several invasive neurostimulation modalities available today and several less invasive modalities under investigation. Clinicians will soon face a choice that should not be made randomly. We introduce the concept of a prestimulation evaluation protocol, consisting of a series of rationally chosen investigations that evaluate the presence of biomarkers for response to various neurostimulation therapies. These biomarkers should reflect the susceptibility of the individuals epileptic network to a given neurostimulation technique. This will require elucidation of the specific mechanism(s) of action of the different neurostimulation modalities. This manuscript provides a hypothetical framework that may be more applicable in the near future when pre-clinical research progresses and can be translated into human applications.

Clinical vagus nerve stimulation paradigms induce pronounced brain and body hypothermia in rats

Vagus nerve stimulation (VNS) is a widely used neuromodulation technique that is currently used or being investigated as therapy for a wide array of human diseases such as epilepsy, depression, Alzheimers disease, tinnitus, inflammatory diseases, pain, heart failure and many others. Here, we report a pronounced decrease in brain and core temperature during VNS in freely moving rats. Two hours of rapid cycle VNS (7s on/18s off) decreased brain temperature by around [Formula: see text]C, while standard cycle VNS (30[Formula: see text]s on/300[Formula: see text]s off) was associated with a decrease of around [Formula: see text]C. Rectal temperature similarly decreased by more than [Formula: see text]C during rapid cycle VNS. The hypothermic effect triggered by VNS was further associated with a vasodilation response in the tail, which reflects an active heat release mechanism. Despite previous evidence indicating an important role of the locus coeruleus-noradrenergic system in therapeutic effects of VNS, lesioning this system with the noradrenergic neurotoxin DSP-4 did not attenuate the hypothermic effect. Since body and brain temperature affect most physiological processes, this finding is of substantial importance for interpretation of several previously published VNS studies and for the future direction of research in the field.

Closed loop neurostimulation for epilepsy

Various neurostimulation modalities have emerged in the field of epilepsy. Despite the fact that delivery of an electrical current to the hyperexcitable epileptic brain might, at first, seem contradictory, neurostimulation has become an established therapeutic option with a promising efficacy and adverse effects profile. In “responsive” neurostimulation the strategy is to interfere as early as possible with the accumulation of seizure activity to prematurely abort or prevent an upcoming seizure. The design of technology required for responsive stimulation is more challenging compared to devices for open-loop neurostimulation. The achievement of therapeutic success is dependent on adequate sensing and stimulation algorithms and a fast coupling between both. The benefits of delivering current only at the time of an approaching seizure merit further investigation. Current experience with responsive neurostimulation in epilepsy is still limited, but seems promising.

TDM based dose optimization of piperacillin and meropenem: a randomized controlled trial

ESICM LIVES 2012 25th Annual Congress Lisbon, Portugal 13–17 October This supplement issue of the official ESICM/ESPNIC journal Intensive Care Medicine contains abstracts of scientific papers presented at the 25th Annual Congress of the European Society of Intensive Care Medicine. The abstracts appear in order of presentation from Monday 15 October to Wednesday 17 October 2012. The same abstract numbering is used in the Congress Final Programme. This supplement was not sponsored by outside commercial interests; it was funded entirely by the society’s own resources. DOI:10.1007/s00134-012-2683-0 123 25th ANNUAL CONGRESS, CCL, LISBON-PORTUGAL, 13-17 OCTOBER 2012 25th ANNUAL CONGRESS, CCL, LISBON-PORTUGAL, 13-17 OCTOBER 2012 25th ANNUAL CONGRESS, CCL, LISBON-PORTUGAL, 13-17 OCTOBER 2012